Prospects for the application of gene sequencing technology in the next 40 years.

Researchers are increasingly demanding genetic sequencing data.
Eric Green, Edward Rubin and Maynard Olson look ahead to the use of gene sequencing technology over the next 40 years.
40 years ago, before 1997, two papers first reported on the simple method of determining the sequence of chemical bases in DNA fragments.
until then, molecular biologists could only detect DNA fragments, not bases.
since then, the development of DNA sequencing technology has evolved thousands of miles from the very beginning of simple detection to high-throughput sequencing today.
data generation has grown exponentially over the past 30 years, while data generation has grown exponentially over the past 10 years as a result of high-throughput sequencing.
, the data produced by gene sequencing has revolutionized a wide range of applications in a wide range of fields, including archaeology, criminal investigation, and prenatal diagnosis.
, what will be the development of genetic sequencing in the next 40 years? Predictors are often wrong about which technologies (or, more importantly, which applications) will be the most revolutionary.
in the early days of the Internet, few predicted that e-mail would become globally available.
, neither Wall Street traders nor Silicon Valley investors foresaw that games, online video and social media would become the "troika" of today's networks.
While our predictions about the future of DNA sequencing have not been better, we are good at providing a thoughtful framework.
our core view is that the development of DNA sequencing will be driven by killer applications, not killer technology. improvements in
demand technology can increase or decrease demand.
as Bill Gates once cited as an example: as tire designs become more durable, demand for tires will diminish, eventually causing the tire industry to shrink.
but we believe that the development of DNA sequencing will follow the model of computers and cameras, not the development of tires.
as costs decrease and speed up, the use of DNA sequencing will increase and demand will increase (figure "Better, Faster, Cheaper").
as DNA sequencing moves from the laboratory to clinical, consumer and other areas, the development of DNA sequencing will follow the "more supply means more demand" rule.
researchers' demand for genetic sequencing data is growing.
in the 1990s, sequencing the human genome seemed like an impossible task.
Now, geneticists want to sequence every stage of development, including epigenetic modification, in every cell in every tissue on Earth.
they also hope to obtain a comprehensive gene expression spectrum by sequencing complementary DNA copies of messenger RNA molecules.
at the same time, archaeologists began using DNA sequencing to reconstruct the genetic drifts of human ancestors, just as previously deduced the evolution of language, cultural customs and matter.
ecologists, microbiologists and evolutionary biologists also want to use DNA sequencing techniques to analyze the genomes of all living species, including extinct species, and even ecosystems.
clearly, the ongoing demand for data will require large-scale data interpretation.
current, the bottleneck in DNA sequencing is the analysis and interpretation of data.
But just as new informatics methods and a large number of data sets have significantly improved language translation and image recognition, we predict that the combination of a large number of DNA sequence datasets with phenotype information will allow researchers to infer the biological functions corresponding to each genome sequence.
more important, most of the basic science needed to interpret the data has been applied to practical applications (such as high-quality reference sequences of bacterial genomes, or the rules under which certain genetic networks operate in healthy populations).
, for example, identifying microbial DNA sequences in environmental or clinical samples, or identifying genetic mutations associated with known biological phenotypes.
killer applications over the years, the platform for DNA sequencing has changed dramatically ("The advance of the sequencing platform - multiple METHODs of DNA sequencing").
However, judging by the trajectory of similar technologies that seem to never be met, such as smartphones, computers and cameras, it will be the application, not the technology itself, that will really drive the development of DNA sequencing.
we are convinced that DNA sequencing will have a revolutionary impact in medicine.
in clinical applications, the most breakthrough in DNA sequencing is the detection of prenatal tests for abnormal chromosome counts, such as the 21-third body that causes Down's syndrome, for frequency of use alone.
this genetic screening relies on a small amount of cellless fetal DNA that detects circulation in the mother's blood.
participants in the Human Genome Project did not expect down screening to be "the fastest-growing genetic test in medical history."
in fact, experts in the field estimate that about 4 to 6 million pregnant women worldwide receive the test each year, more than 15 million in a decade.
Given that such tests are non-invasive, easy to perform, and require low level accuracy of nucleotides (the number of chromosomes assessment stakes can not require an assessment of genetic mutations), such tests may make a big difference in future primary care.
in high-income countries, genome sequencing has been used to detect children with under-studied congenital diseases.
30 percent of the time, genetic testing can detect disease-causing mutations, a number that will rise as DNA sequencing matures to interpret data.
in some cases, the diagnosis of DNA sequencing significantly improves the effectiveness of treatment.
more important, genetic testing is more accurate, thus eliminating the need for patients and doctors to eliminate possible diseases.
in oncology, a significant investment is flowing into the field of liquid biopsy development.
liquid biopsy technology will develop into a routine tool for cancer screening, just as pap smears and colonoscopies are commonly used today.
with the emergence of cancer treatment for specific mutations, rather than tumor types, fluid biopsy can ultimately guide treatment interventions, even if the exact location of the tumor cannot be found, and the presence of the tumor can only be determined by DNA analysis of the blood sample.
fact, there is a lot to be used in DNA sequencing beyond clinical practice, such as hand-held DNA sequencers.
epidemiologists can use hand-held sequencers to detect air, water, food, animals and insects, not to mention human pharynx and body fluids.
in fact, in low- and middle-income countries, this simple DNA sequencer has led the Global Virus Hemic project.
the aim is to sequence many wild animal DNA samples to identify viruses that can spread to humans and cause disease.
, public health experts are also discussing how to monitor disease outbreaks by sequencing microbes in urban waste.
marine biologists are exploring how to monitor the marine ecosystem through systematic macrogenomics research.
in the field of justice, portable DNA sequencers can take DNA analysis out of the lab, making DNA sequencing a first-line police tool.
police may "read" people's DNA, just as they now check their license plates or identification documents.
the fact that cheap and easy DNA sequencing could lead to mass surveillance has recently attracted the attention of human rights groups.
at home, DNA sequencing devices could be the next "smart" or "connected" device after smoke alarms and thermostats.
even suggested that the bathroom was the ideal place to monitor the health of a family through real-time DNA sequencing. what is a stumbling block to the development of DNA sequencing
the ceiling? In just 40 years, the core goal of the practical application of cellular molecular data has changed from getting information itself to meta-informational.
take the clinical application of gene sequencing as an example.
may in the near future, DNA sequencing will become a regular tool for body fluid analysis. the problem,
, however, is that data from millions of years of medical history must be carefully organized to provide a framework for interpreting meta-information to identify which data should be retained and which should be dug deep.
on medicine, we agree with the recommendation of advisory groups such as the National Research Council's Precision Medicine Committee that the world needs to create a broad "information-sharing body."
this will cover the molecular and clinical data of genome sequencing of millions of human reproductive cells.
there are a number of projects that are currently working on such large-scale population work, including the UK Biobank Resource and the US All Us Research Program.
here we give the best guess.
surprise is certain.
in fact, for decades from now, most of the world's data (now stored on hard drives or in the go) can be stored in DNA, and the main driving force behind DNA sequencing is not the diagnosis and treatment of diseases, but our urgent need for data storage.
the advances of the sequencing platform - a variety of DNA sequencing methods have been updated several times over the past 40 years.
1985, almost all DNA sequencing was done using Sanger or double deoxygenation chain termination: reaction products were labeled with radioactive nucleotides, separated on acrylamide plate gels, and detected with radiation self-development (radioactive markers in samples detected with X-rays or photographic film).
by 2000, the tetrachofic fluorescence method became mainstream: using end-chain reaction nucleotide analogues to mark reaction products, electrophoretic separation in capillaries filled with jelly-like media, and detection with energy-shifting fluorescent dyes.
by 2010, sequencing technology is more diverse.
the main methods are chemical methods based on large-scale parallel analysis of DNA cloning (clone amplification of individual DNA molecules) and edge-synthetic edge sequencing (these methods rely on reversible chain terminators).
from now on, the performance of each DNA sequencing platform will depend on its purpose.
in oncology and medical genetics, the goal is usually to correctly identify each gene and define each mutation that exists in multiple copies.
by contrast, in applications that require only knowing whether to match a particular sequence, such as species recognition, portable quickness is a top priority, and accuracy is less important. In addition, the relative need sedation and decentralization of DNA sequencing may also change
.
for example, an epidemiologist who tries to assess the impact of the virus on a particular village in Sierra Leone in real time may need cheap portable equipment.
but for those who need to generate large data sets, shipping samples to a centralized, commercially operated DNA sequencing center can be more efficient and cost-effective, especially for applications that require strict quality control and sample tracking," such as clinical applications.
Source: The Mystery of Life.